Objective. To compare the pattern of antibody responses to Borrelia burgdorferi in patients with antibiotic-refractory, antibiotic-responsive, or nonantibiotic-treated Lyme arthritis as an indirect measure of spirochetal persistence or eradication.Methods. At least 3 serial serum samples from 41 patients with antibiotic-refractory arthritis and 23 patients with antibiotic-responsive arthritis, and samples from 10 non-antibiotic-treated, historical control patients were tested for IgG reactivity with B burgdorferi sonicate and 4 differentially expressed outer surface lipoproteins of the spirochete, by enzyme-linked immunosorbent assay.Results. Among non-antibiotic-treated patients, antibody titers to B burgdorferi antigens remained high throughout a 2-5-year period of arthritis. In contrast, in patients with antibiotic-responsive arthritis, in whom joint swelling usually resolved during a 1-month course of oral antibiotic therapy, the median antibody titers to most of the spirochetal antigens remained steady or decreased during the first 1-3 months after starting antibiotic therapy. In patients with antibiotic-refractory arthritis, who had persistent joint swelling for a median duration of 10 months despite 2-3 months of oral or intravenous antibiotics, the median titers to most antigens increased slightly during the first 1-3 months. However, by 4-6 months after starting antibiotic therapy, reactivity with all antigens declined similarly in both antibiotic-treated groups.Conclusion. Whereas the antibody titers to B burgdorferi remained high in non-antibiotic-treated patients, the titers declined similarly 4-6 months after starting therapy in patients with antibiotic-responsive or antibiotic-refractory arthritis, suggesting that synovial inflammation persisted in patients with antibioticrefractory arthritis after the period of infection.

Synovitis in patients with antibiotic-refractory Lyme arthritis persists for months to several years after antibiotic therapy. This course, which may result from infection-induced autoimmunity, is associated with T cell recognition of Borrelia burgdorferi outer surface protein A (OspA161–175) and with HLA-DR molecules that bind this epitope, including the DRB1*0401 molecule. In this study, we used tetramer reagents to determine the frequencies of OspA161–175-specific T cells in samples of PBMC and synovial fluid mononuclear cells (SFMC) from 13 DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory arthritis. Initially, three of the six patients (50%) with antibiotic-responsive arthritis and four of the seven patients (57%) with antibiotic-refractory arthritis had frequencies of OspA161–175-specific CD4+ T cells in peripheral blood above the cutoff value of 4 per 105 cells. Among the five patients with concomitant PBMC and SFMC, four (80%) had OspA tetramer-positive cells at both sites, but the mean frequency of such cells was 16 times higher in SFMC, reaching levels as high as 1,177 per 105 cells. In the two patients in each patient group in whom serial samples were available, the frequencies of OspA161–175-specific T cells declined to low or undetectable levels during or soon after antibiotic therapy, months before the resolution of synovitis in the two patients with antibiotic-refractory arthritis. Thus, the majority of patients with Lyme arthritis initially have increased frequencies of OspA161–175-specific T cells. However, the marked decline in the frequency of such cells with antibiotic therapy suggests that persistent synovitis in the refractory group is not perpetuated by these cells.